Patrice Wendling

TORONTO – Contrary to conventional thinking, a high respiratory syncytial viral load may be protective against progression of bronchiolitis.

Elevated respiratory syncytial viral (RSV) load was unexpectedly associated with less severe bronchiolitis disease in a convenience sample of 63 children less than 2 years of age who presented to an ED with clinical signs of infection.

Children with an elevated respiratory syncytial viral load were more likely to be discharged home, to require less than 24 hours of intravenous fluids, and to not require intubation, Dr. Berkeley L. Bennett and associates reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

While these trends did not reach statistical significance, there was a highly significant association between higher RSV load and the need for more than 24 hours of oxygen therapy.

RSV load had an independent and protective effect on duration of oxygen therapy in a stepwise multivariate regression analysis that included RSV load, age, duration of illness, interleukin-8 (IL-8), and interleukin-10 (IL-10). A 10-fold increase in RSV load decreased the need for more than 24 hours of oxygen therapy by 43%.

“We hypothesize that an adequate viral load is necessary to induce an optimal inflammatory response that is capable of controlling the disease,” Dr. Bennett of Cincinnati Children's Hospital Medical Center, said in an interview. “Alternatively, with a small amount of viral load, you get a weak inflammatory response, and the disease will smolder and go unchecked.”

Nasal-wash samples obtained from 101 children prospectively enrolled during the RSV season between November 2004 and February 2005 were analyzed for viral pathogens via cell culture, RSV quantification via plaque assay, and cytokine and chemokine concentrations via the Bio-Plex Suspension Array System.

Of these, 63 were RSV positive and included for analysis. Twenty-two were discharged home from the ED and 41 were admitted in this study that was published simultaneously in the May 15 issue of the Journal of Infectious Diseases (J. Infect. Dis. 2007;195: 1532-40).

The mean RSV concentration was 3.95 log10 copies/mL (range 1.0-6.85 log10 copies/mL). Rather than using a numeric definition for an “elevated” viral load, the mean viral concentration was compared between groups, said Dr. Bennett, who conducted the study while at Baylor College of Medicine, Houston.

RSV load was directly correlated with age and inversely correlated with duration of illness at presentation. The investigators analyzed the patients in four age categories, and found viral load increased with age.

RSV load was significantly directly correlated to IL-8 and IL-10 concentrations.

“If an adequate level of RSV concentration is truly necessary to induce an optimal inflammatory response, that may explain why previous antiviral and anti-inflammatory therapies have not been as beneficial as hoped,” Dr. Bennett said.

She acknowledged that the study was limited by its cross-sectional design and single nasal-wash sampling; trials are needed that will analyze different samples at different time points.

We hypothesize that an adequate viral load is needed to induce an optimal inflammatory response. DR. BENNETT

TORONTO – Contrary to conventional thinking, a high respiratory syncytial viral load may be protective against progression of bronchiolitis.

Elevated respiratory syncytial viral (RSV) load was unexpectedly associated with less severe bronchiolitis disease in a convenience sample of 63 children less than 2 years of age who presented to an ED with clinical signs of infection.

Children with an elevated respiratory syncytial viral load were more likely to be discharged home, to require less than 24 hours of intravenous fluids, and to not require intubation, Dr. Berkeley L. Bennett and associates reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

While these trends did not reach statistical significance, there was a highly significant association between higher RSV load and the need for more than 24 hours of oxygen therapy.

RSV load had an independent and protective effect on duration of oxygen therapy in a stepwise multivariate regression analysis that included RSV load, age, duration of illness, interleukin-8 (IL-8), and interleukin-10 (IL-10). A 10-fold increase in RSV load decreased the need for more than 24 hours of oxygen therapy by 43%.

“We hypothesize that an adequate viral load is necessary to induce an optimal inflammatory response that is capable of controlling the disease,” Dr. Bennett of Cincinnati Children's Hospital Medical Center, said in an interview. “Alternatively, with a small amount of viral load, you get a weak inflammatory response, and the disease will smolder and go unchecked.”

Nasal-wash samples obtained from 101 children prospectively enrolled during the RSV season between November 2004 and February 2005 were analyzed for viral pathogens via cell culture, RSV quantification via plaque assay, and cytokine and chemokine concentrations via the Bio-Plex Suspension Array System.

Of these, 63 were RSV positive and included for analysis. Twenty-two were discharged home from the ED and 41 were admitted in this study that was published simultaneously in the May 15 issue of the Journal of Infectious Diseases (J. Infect. Dis. 2007;195: 1532-40).

The mean RSV concentration was 3.95 log10 copies/mL (range 1.0-6.85 log10 copies/mL). Rather than using a numeric definition for an “elevated” viral load, the mean viral concentration was compared between groups, said Dr. Bennett, who conducted the study while at Baylor College of Medicine, Houston.

RSV load was directly correlated with age and inversely correlated with duration of illness at presentation. The investigators analyzed the patients in four age categories, and found viral load increased with age.

RSV load was significantly directly correlated to IL-8 and IL-10 concentrations.

“If an adequate level of RSV concentration is truly necessary to induce an optimal inflammatory response, that may explain why previous antiviral and anti-inflammatory therapies have not been as beneficial as hoped,” Dr. Bennett said.

She acknowledged that the study was limited by its cross-sectional design and single nasal-wash sampling; trials are needed that will analyze different samples at different time points.

We hypothesize that an adequate viral load is needed to induce an optimal inflammatory response. DR. BENNETT

TORONTO – Contrary to conventional thinking, a high respiratory syncytial viral load may be protective against progression of bronchiolitis.

Elevated respiratory syncytial viral (RSV) load was unexpectedly associated with less severe bronchiolitis disease in a convenience sample of 63 children less than 2 years of age who presented to an ED with clinical signs of infection.

Children with an elevated respiratory syncytial viral load were more likely to be discharged home, to require less than 24 hours of intravenous fluids, and to not require intubation, Dr. Berkeley L. Bennett and associates reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

While these trends did not reach statistical significance, there was a highly significant association between higher RSV load and the need for more than 24 hours of oxygen therapy.

RSV load had an independent and protective effect on duration of oxygen therapy in a stepwise multivariate regression analysis that included RSV load, age, duration of illness, interleukin-8 (IL-8), and interleukin-10 (IL-10). A 10-fold increase in RSV load decreased the need for more than 24 hours of oxygen therapy by 43%.

“We hypothesize that an adequate viral load is necessary to induce an optimal inflammatory response that is capable of controlling the disease,” Dr. Bennett of Cincinnati Children's Hospital Medical Center, said in an interview. “Alternatively, with a small amount of viral load, you get a weak inflammatory response, and the disease will smolder and go unchecked.”

Nasal-wash samples obtained from 101 children prospectively enrolled during the RSV season between November 2004 and February 2005 were analyzed for viral pathogens via cell culture, RSV quantification via plaque assay, and cytokine and chemokine concentrations via the Bio-Plex Suspension Array System.

Of these, 63 were RSV positive and included for analysis. Twenty-two were discharged home from the ED and 41 were admitted in this study that was published simultaneously in the May 15 issue of the Journal of Infectious Diseases (J. Infect. Dis. 2007;195: 1532-40).

The mean RSV concentration was 3.95 log10 copies/mL (range 1.0-6.85 log10 copies/mL). Rather than using a numeric definition for an “elevated” viral load, the mean viral concentration was compared between groups, said Dr. Bennett, who conducted the study while at Baylor College of Medicine, Houston.

RSV load was directly correlated with age and inversely correlated with duration of illness at presentation. The investigators analyzed the patients in four age categories, and found viral load increased with age.

RSV load was significantly directly correlated to IL-8 and IL-10 concentrations.

“If an adequate level of RSV concentration is truly necessary to induce an optimal inflammatory response, that may explain why previous antiviral and anti-inflammatory therapies have not been as beneficial as hoped,” Dr. Bennett said.

She acknowledged that the study was limited by its cross-sectional design and single nasal-wash sampling; trials are needed that will analyze different samples at different time points.

We hypothesize that an adequate viral load is needed to induce an optimal inflammatory response. DR. BENNETT

TORONTO – The investigational drug motavizumab may offer high-risk infants additional protection against respiratory syncytial virus disease, Dr. Xavier Carbonell-Estrany reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

Motavizumab demonstrated noninferiority to palivizumab with a 26% relative reduction in the primary end point of respiratory syncytial virus (RSV) hospitalizations in a phase III multicenter study with 6,635 preterm infants, the investigators wrote.

The overall incidence of hospitalization was low in both groups: 1.4% for patients treated with motavizumab and 1.9% for those treated with palivizumab.

Additionally, in a subset of patients, motavizumab significantly reduced the secondary end point of outpatient medically attended lower respiratory tract infections (LRIs) by 50%, compared with palivizumab: 2% of 1,227 patients vs. 4% of 1,183 patients.

Motavizumab (Numax) is an enhanced-potency, RSV-specific, humanized monoclonal antibody that has shown a similar safety and pharmacokinetic profile in phase I and II trials to palivizumab (Synagis), an RSV-specific monoclonal antibody that is the standard of care for infants at high-risk for RSV, they said.

MedImmune Inc., which markets palivizumab and is developing motavizumab, sponsored the trial. Dr. Carbonell-Estrany is a member of the steering committee of the Motavizumab Study Group and was acting as consultant on this occasion for MedImmune.

“I am very pleased with the study results for motavizumab,” lead author Dr. Carbonell-Estrany, chair of neonatology at the University of Barcelona's Hospital Clinic and vice president of the Spanish Neonatal Society, said in a statement. “As a practicing neonatologist, I look forward to the potential to use this next-generation antibody to help reduce RSV-related hospitalizations and LRIs in the outpatient setting.”

The study was conducted at 347 centers in 24 countries.

It included both infants who were 6 months of age or younger at the time of randomization with a gestational age of 35 weeks or fewer at birth, and children who were 24 months of age or younger with a diagnosis of chronic lung disease of prematurity requiring treatment within 6 months before the time of randomization.

Over two consecutive RSV seasons, 6,635 patients were randomized to receive motavizumab or palivizumab 15 mg/kg intramuscularly monthly, with 150 days of follow-up. Each child participated in the study for a single RSV season.

A total of 3,329 children were randomized to motavizumab and 3,306 to palivizumab.

Overall, 59 motavizumab patients and 60 palivizumab patients were lost to follow-up, had consent withdrawn, or died.

No death was considered to be related to the study drugs, and there were no RSV-related deaths.

The most frequently reported cause of death in both groups was SIDS, with four in the motavizumab and two in the palivizumab group.

Drug-related adverse events were comparable between the motavizumab group and the palivizumab group (258 vs. 298), as were drug discontinuations (10 vs. 13).

Injection site reactions were more common in the motavizumab group than the palivizumab group (110 vs. 89), the authors reported.

TORONTO – The investigational drug motavizumab may offer high-risk infants additional protection against respiratory syncytial virus disease, Dr. Xavier Carbonell-Estrany reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

Motavizumab demonstrated noninferiority to palivizumab with a 26% relative reduction in the primary end point of respiratory syncytial virus (RSV) hospitalizations in a phase III multicenter study with 6,635 preterm infants, the investigators wrote.

The overall incidence of hospitalization was low in both groups: 1.4% for patients treated with motavizumab and 1.9% for those treated with palivizumab.

Additionally, in a subset of patients, motavizumab significantly reduced the secondary end point of outpatient medically attended lower respiratory tract infections (LRIs) by 50%, compared with palivizumab: 2% of 1,227 patients vs. 4% of 1,183 patients.

Motavizumab (Numax) is an enhanced-potency, RSV-specific, humanized monoclonal antibody that has shown a similar safety and pharmacokinetic profile in phase I and II trials to palivizumab (Synagis), an RSV-specific monoclonal antibody that is the standard of care for infants at high-risk for RSV, they said.

MedImmune Inc., which markets palivizumab and is developing motavizumab, sponsored the trial. Dr. Carbonell-Estrany is a member of the steering committee of the Motavizumab Study Group and was acting as consultant on this occasion for MedImmune.

“I am very pleased with the study results for motavizumab,” lead author Dr. Carbonell-Estrany, chair of neonatology at the University of Barcelona's Hospital Clinic and vice president of the Spanish Neonatal Society, said in a statement. “As a practicing neonatologist, I look forward to the potential to use this next-generation antibody to help reduce RSV-related hospitalizations and LRIs in the outpatient setting.”

The study was conducted at 347 centers in 24 countries.

It included both infants who were 6 months of age or younger at the time of randomization with a gestational age of 35 weeks or fewer at birth, and children who were 24 months of age or younger with a diagnosis of chronic lung disease of prematurity requiring treatment within 6 months before the time of randomization.

Over two consecutive RSV seasons, 6,635 patients were randomized to receive motavizumab or palivizumab 15 mg/kg intramuscularly monthly, with 150 days of follow-up. Each child participated in the study for a single RSV season.

A total of 3,329 children were randomized to motavizumab and 3,306 to palivizumab.

Overall, 59 motavizumab patients and 60 palivizumab patients were lost to follow-up, had consent withdrawn, or died.

No death was considered to be related to the study drugs, and there were no RSV-related deaths.

The most frequently reported cause of death in both groups was SIDS, with four in the motavizumab and two in the palivizumab group.

Drug-related adverse events were comparable between the motavizumab group and the palivizumab group (258 vs. 298), as were drug discontinuations (10 vs. 13).

Injection site reactions were more common in the motavizumab group than the palivizumab group (110 vs. 89), the authors reported.

TORONTO – The investigational drug motavizumab may offer high-risk infants additional protection against respiratory syncytial virus disease, Dr. Xavier Carbonell-Estrany reported in a poster presentation at the annual meeting of the Pediatric Academic Societies.

Motavizumab demonstrated noninferiority to palivizumab with a 26% relative reduction in the primary end point of respiratory syncytial virus (RSV) hospitalizations in a phase III multicenter study with 6,635 preterm infants, the investigators wrote.

The overall incidence of hospitalization was low in both groups: 1.4% for patients treated with motavizumab and 1.9% for those treated with palivizumab.

Additionally, in a subset of patients, motavizumab significantly reduced the secondary end point of outpatient medically attended lower respiratory tract infections (LRIs) by 50%, compared with palivizumab: 2% of 1,227 patients vs. 4% of 1,183 patients.

Motavizumab (Numax) is an enhanced-potency, RSV-specific, humanized monoclonal antibody that has shown a similar safety and pharmacokinetic profile in phase I and II trials to palivizumab (Synagis), an RSV-specific monoclonal antibody that is the standard of care for infants at high-risk for RSV, they said.

MedImmune Inc., which markets palivizumab and is developing motavizumab, sponsored the trial. Dr. Carbonell-Estrany is a member of the steering committee of the Motavizumab Study Group and was acting as consultant on this occasion for MedImmune.

“I am very pleased with the study results for motavizumab,” lead author Dr. Carbonell-Estrany, chair of neonatology at the University of Barcelona's Hospital Clinic and vice president of the Spanish Neonatal Society, said in a statement. “As a practicing neonatologist, I look forward to the potential to use this next-generation antibody to help reduce RSV-related hospitalizations and LRIs in the outpatient setting.”

The study was conducted at 347 centers in 24 countries.

It included both infants who were 6 months of age or younger at the time of randomization with a gestational age of 35 weeks or fewer at birth, and children who were 24 months of age or younger with a diagnosis of chronic lung disease of prematurity requiring treatment within 6 months before the time of randomization.

Over two consecutive RSV seasons, 6,635 patients were randomized to receive motavizumab or palivizumab 15 mg/kg intramuscularly monthly, with 150 days of follow-up. Each child participated in the study for a single RSV season.

A total of 3,329 children were randomized to motavizumab and 3,306 to palivizumab.

Overall, 59 motavizumab patients and 60 palivizumab patients were lost to follow-up, had consent withdrawn, or died.

No death was considered to be related to the study drugs, and there were no RSV-related deaths.

The most frequently reported cause of death in both groups was SIDS, with four in the motavizumab and two in the palivizumab group.

Drug-related adverse events were comparable between the motavizumab group and the palivizumab group (258 vs. 298), as were drug discontinuations (10 vs. 13).

Injection site reactions were more common in the motavizumab group than the palivizumab group (110 vs. 89), the authors reported.

CHICAGO – Valsartan significantly reduced both systolic and diastolic blood pressure without significant adverse events in the first trial of an angiotensin II receptor blocker in children younger than 6 years.

Valsartan is indicated for the treatment of hypertension and heart failure in adults, but had never been studied in children. In November 2006, the Food and Drug Administration approved safety labeling revisions for valsartan tablets to advise of the risk of fetal and neonatal morbidity when used by pregnant women.

Dr. Joseph Flynn and associates presented preliminary results in a poster at the annual meeting of the American Society of Hypertension from a multicenter, placebo-controlled study evaluating three doses of valsartan in 90 children with a mean seated systolic BP greater than or equal to the 95th percentile of the National High Blood Pressure Education Program normative BP values for children.

After a 1-week placebo washout screening phase, the children were randomized to low, medium, and high doses of valsartan for 2 weeks (phase 1), then rerandomized to placebo or valsartan for 2 more weeks (phase 2).

In phase 1, the doses were 5, 20, or 40 mg/day for those children weighing less than 18 kg, and 10, 40, or 80 mg/day for those weighing more than 18 kg. Half of the children stayed on the same dose in phase 2, and half were withdrawn to placebo.

At admission, the children's mean age was 3 years; 60% were boys, and 30% were black. Most children (79%) had hypertension related to renal disease; some (3%) were hypertensive because of heart disease, and 18% because of other causes.

In phase 1, valsartan significantly reduced both systolic and diastolic BP at all three doses, reported Dr Flynn, who conducted the study while at Children's Hospital at Montefiore, New York, and is now a professor of pediatrics at Children's Hospital and Regional Medical Center, in Seattle.

In phase 2, systolic and diastolic BP was significantly lower in children receiving valsartan, compared with those receiving placebo. The mean difference between valsartan and placebo was −4.1 mm Hg for systolic BP and −3.7 mm Hg for diastolic.

“Since many of these children have hypertension due to underlying renal disease, valsartan may be well suited for treatment of hypertension in this age group,” Dr. Flynn said in an interview.

Adverse events, such as cold symptoms, were minor and were similar between the different dose groups, he said. In all, 29% of children experienced an adverse event in phase 1 and 39% in phase 2. No participants discontinued treatment because of an adverse event.

The investigators will undertake a further analysis of the 1-year open-label extension phase of the study to learn how well valsartan worked over a longer period of time. Studies of valsartan in children with proteinuria are also planned to evaluate its safety and effectiveness in reducing proteinuria.

CHICAGO – Valsartan significantly reduced both systolic and diastolic blood pressure without significant adverse events in the first trial of an angiotensin II receptor blocker in children younger than 6 years.

Valsartan is indicated for the treatment of hypertension and heart failure in adults, but had never been studied in children. In November 2006, the Food and Drug Administration approved safety labeling revisions for valsartan tablets to advise of the risk of fetal and neonatal morbidity when used by pregnant women.

Dr. Joseph Flynn and associates presented preliminary results in a poster at the annual meeting of the American Society of Hypertension from a multicenter, placebo-controlled study evaluating three doses of valsartan in 90 children with a mean seated systolic BP greater than or equal to the 95th percentile of the National High Blood Pressure Education Program normative BP values for children.

After a 1-week placebo washout screening phase, the children were randomized to low, medium, and high doses of valsartan for 2 weeks (phase 1), then rerandomized to placebo or valsartan for 2 more weeks (phase 2).

In phase 1, the doses were 5, 20, or 40 mg/day for those children weighing less than 18 kg, and 10, 40, or 80 mg/day for those weighing more than 18 kg. Half of the children stayed on the same dose in phase 2, and half were withdrawn to placebo.

At admission, the children's mean age was 3 years; 60% were boys, and 30% were black. Most children (79%) had hypertension related to renal disease; some (3%) were hypertensive because of heart disease, and 18% because of other causes.

In phase 1, valsartan significantly reduced both systolic and diastolic BP at all three doses, reported Dr Flynn, who conducted the study while at Children's Hospital at Montefiore, New York, and is now a professor of pediatrics at Children's Hospital and Regional Medical Center, in Seattle.

In phase 2, systolic and diastolic BP was significantly lower in children receiving valsartan, compared with those receiving placebo. The mean difference between valsartan and placebo was −4.1 mm Hg for systolic BP and −3.7 mm Hg for diastolic.

“Since many of these children have hypertension due to underlying renal disease, valsartan may be well suited for treatment of hypertension in this age group,” Dr. Flynn said in an interview.

Adverse events, such as cold symptoms, were minor and were similar between the different dose groups, he said. In all, 29% of children experienced an adverse event in phase 1 and 39% in phase 2. No participants discontinued treatment because of an adverse event.

The investigators will undertake a further analysis of the 1-year open-label extension phase of the study to learn how well valsartan worked over a longer period of time. Studies of valsartan in children with proteinuria are also planned to evaluate its safety and effectiveness in reducing proteinuria.

CHICAGO – Valsartan significantly reduced both systolic and diastolic blood pressure without significant adverse events in the first trial of an angiotensin II receptor blocker in children younger than 6 years.

Valsartan is indicated for the treatment of hypertension and heart failure in adults, but had never been studied in children. In November 2006, the Food and Drug Administration approved safety labeling revisions for valsartan tablets to advise of the risk of fetal and neonatal morbidity when used by pregnant women.

Dr. Joseph Flynn and associates presented preliminary results in a poster at the annual meeting of the American Society of Hypertension from a multicenter, placebo-controlled study evaluating three doses of valsartan in 90 children with a mean seated systolic BP greater than or equal to the 95th percentile of the National High Blood Pressure Education Program normative BP values for children.

After a 1-week placebo washout screening phase, the children were randomized to low, medium, and high doses of valsartan for 2 weeks (phase 1), then rerandomized to placebo or valsartan for 2 more weeks (phase 2).

In phase 1, the doses were 5, 20, or 40 mg/day for those children weighing less than 18 kg, and 10, 40, or 80 mg/day for those weighing more than 18 kg. Half of the children stayed on the same dose in phase 2, and half were withdrawn to placebo.

At admission, the children's mean age was 3 years; 60% were boys, and 30% were black. Most children (79%) had hypertension related to renal disease; some (3%) were hypertensive because of heart disease, and 18% because of other causes.

In phase 1, valsartan significantly reduced both systolic and diastolic BP at all three doses, reported Dr Flynn, who conducted the study while at Children's Hospital at Montefiore, New York, and is now a professor of pediatrics at Children's Hospital and Regional Medical Center, in Seattle.

In phase 2, systolic and diastolic BP was significantly lower in children receiving valsartan, compared with those receiving placebo. The mean difference between valsartan and placebo was −4.1 mm Hg for systolic BP and −3.7 mm Hg for diastolic.

“Since many of these children have hypertension due to underlying renal disease, valsartan may be well suited for treatment of hypertension in this age group,” Dr. Flynn said in an interview.

Adverse events, such as cold symptoms, were minor and were similar between the different dose groups, he said. In all, 29% of children experienced an adverse event in phase 1 and 39% in phase 2. No participants discontinued treatment because of an adverse event.

The investigators will undertake a further analysis of the 1-year open-label extension phase of the study to learn how well valsartan worked over a longer period of time. Studies of valsartan in children with proteinuria are also planned to evaluate its safety and effectiveness in reducing proteinuria.

CHICAGO – Combining the calcium channel blocker amlodipine with the angiotensin receptor blocker olmesartan provides greater reductions in blood pressure than does either agent used as monotherapy, Dr. Steven G. Chrysant said at the annual meeting of the American Society of Hypertension.

Daiichi Sankyo Inc. filed a new drug application in November 2006 for a fixed-dose combination of the two antihypertensives.

Known as Azor, this investigational agent is currently under regulatory and trade name review in the United States.

Lead investigator Dr. Chrysant reported data from a phase III double-blind, placebo-controlled factorial study in which 1,940 patients with mild to severe hypertension were randomized to either monotherapy or co-administration of amlodipine 5-10 mg/day and olmesartan 10-20-40 mg/day for 8 weeks.

Hypertension was defined as seated diastolic BP between 95 mm Hg and 120 mm Hg.

At admission, the average age of patients was 54 years, and their mean blood pressure was 164/102 mm Hg; 13.5% of patients had diabetes, and 34% were hypertensive treatment-naive, said Dr. Chrysant, who reported that he has received grant and research support from the study sponsor, Daiichi Sankyo Pharma Development.

After 8 weeks, all of the combinations of amlodipine and olmesartan resulted in significantly greater blood pressure reductions than either medication alone or placebo, said Dr. Chrysant, a cardiologist at the Oklahoma Cardiovascular and Hypertension Center, University of Oklahoma, Oklahoma City. Blood pressure reductions were dose related.

Amlodipine 10 mg/day plus olmesartan 40 mg/day produced the best results, reducing systolic BP an average of 30.1 mm Hg and diastolic BP an average of 19.0 mm Hg.

In contrast, the average reductions were 19.7/12.7 mm Hg for amlodipine 10 mg alone and 4.8/3.1 mm Hg for placebo.

“Only the high-dose combination dropped the pressure below 140 over 90 [mm Hg],” Dr. Chrysant said at a press briefing.

Adverse events were comparable between groups, occurring in 511 of 970 (53%) combination therapy patients and in 91 of 162 placebo-treated patients (56%). There was one stroke in the olmesartan monotherapy group that was possibly drug related, he said.

Reports of headache, fatigue, and dizziness were highest in the placebo group. The highest incidence of edema (25%) was reported in the amlodipine monotherapy group.

But adding on 40 mg of olmesartan halved this incidence rate, Dr. Chrysant said. He suggests this could be an added benefit of the combination regimen, because many hypertensive patients stop taking their medication because of swollen feet.

Only the high-dose combination dropped the pressure below 140 over 90 mm Hg. DR. CHRYSANT

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO – Combining the calcium channel blocker amlodipine with the angiotensin receptor blocker olmesartan provides greater reductions in blood pressure than does either agent used as monotherapy, Dr. Steven G. Chrysant said at the annual meeting of the American Society of Hypertension.

Daiichi Sankyo Inc. filed a new drug application in November 2006 for a fixed-dose combination of the two antihypertensives.

Known as Azor, this investigational agent is currently under regulatory and trade name review in the United States.

Lead investigator Dr. Chrysant reported data from a phase III double-blind, placebo-controlled factorial study in which 1,940 patients with mild to severe hypertension were randomized to either monotherapy or co-administration of amlodipine 5-10 mg/day and olmesartan 10-20-40 mg/day for 8 weeks.

Hypertension was defined as seated diastolic BP between 95 mm Hg and 120 mm Hg.

At admission, the average age of patients was 54 years, and their mean blood pressure was 164/102 mm Hg; 13.5% of patients had diabetes, and 34% were hypertensive treatment-naive, said Dr. Chrysant, who reported that he has received grant and research support from the study sponsor, Daiichi Sankyo Pharma Development.

After 8 weeks, all of the combinations of amlodipine and olmesartan resulted in significantly greater blood pressure reductions than either medication alone or placebo, said Dr. Chrysant, a cardiologist at the Oklahoma Cardiovascular and Hypertension Center, University of Oklahoma, Oklahoma City. Blood pressure reductions were dose related.

Amlodipine 10 mg/day plus olmesartan 40 mg/day produced the best results, reducing systolic BP an average of 30.1 mm Hg and diastolic BP an average of 19.0 mm Hg.

In contrast, the average reductions were 19.7/12.7 mm Hg for amlodipine 10 mg alone and 4.8/3.1 mm Hg for placebo.

“Only the high-dose combination dropped the pressure below 140 over 90 [mm Hg],” Dr. Chrysant said at a press briefing.

Adverse events were comparable between groups, occurring in 511 of 970 (53%) combination therapy patients and in 91 of 162 placebo-treated patients (56%). There was one stroke in the olmesartan monotherapy group that was possibly drug related, he said.

Reports of headache, fatigue, and dizziness were highest in the placebo group. The highest incidence of edema (25%) was reported in the amlodipine monotherapy group.

But adding on 40 mg of olmesartan halved this incidence rate, Dr. Chrysant said. He suggests this could be an added benefit of the combination regimen, because many hypertensive patients stop taking their medication because of swollen feet.

Only the high-dose combination dropped the pressure below 140 over 90 mm Hg. DR. CHRYSANT

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO – Combining the calcium channel blocker amlodipine with the angiotensin receptor blocker olmesartan provides greater reductions in blood pressure than does either agent used as monotherapy, Dr. Steven G. Chrysant said at the annual meeting of the American Society of Hypertension.

Daiichi Sankyo Inc. filed a new drug application in November 2006 for a fixed-dose combination of the two antihypertensives.

Known as Azor, this investigational agent is currently under regulatory and trade name review in the United States.

Lead investigator Dr. Chrysant reported data from a phase III double-blind, placebo-controlled factorial study in which 1,940 patients with mild to severe hypertension were randomized to either monotherapy or co-administration of amlodipine 5-10 mg/day and olmesartan 10-20-40 mg/day for 8 weeks.

Hypertension was defined as seated diastolic BP between 95 mm Hg and 120 mm Hg.

At admission, the average age of patients was 54 years, and their mean blood pressure was 164/102 mm Hg; 13.5% of patients had diabetes, and 34% were hypertensive treatment-naive, said Dr. Chrysant, who reported that he has received grant and research support from the study sponsor, Daiichi Sankyo Pharma Development.

After 8 weeks, all of the combinations of amlodipine and olmesartan resulted in significantly greater blood pressure reductions than either medication alone or placebo, said Dr. Chrysant, a cardiologist at the Oklahoma Cardiovascular and Hypertension Center, University of Oklahoma, Oklahoma City. Blood pressure reductions were dose related.

Amlodipine 10 mg/day plus olmesartan 40 mg/day produced the best results, reducing systolic BP an average of 30.1 mm Hg and diastolic BP an average of 19.0 mm Hg.

In contrast, the average reductions were 19.7/12.7 mm Hg for amlodipine 10 mg alone and 4.8/3.1 mm Hg for placebo.

“Only the high-dose combination dropped the pressure below 140 over 90 [mm Hg],” Dr. Chrysant said at a press briefing.

Adverse events were comparable between groups, occurring in 511 of 970 (53%) combination therapy patients and in 91 of 162 placebo-treated patients (56%). There was one stroke in the olmesartan monotherapy group that was possibly drug related, he said.

Reports of headache, fatigue, and dizziness were highest in the placebo group. The highest incidence of edema (25%) was reported in the amlodipine monotherapy group.

But adding on 40 mg of olmesartan halved this incidence rate, Dr. Chrysant said. He suggests this could be an added benefit of the combination regimen, because many hypertensive patients stop taking their medication because of swollen feet.

Only the high-dose combination dropped the pressure below 140 over 90 mm Hg. DR. CHRYSANT

ELSEVIER GLOBAL MEDICAL NEWS

KANSAS CITY, MO. — Physicians support using risk-based standing orders for adult hepatitis B vaccinations, but see clear barriers to their implementation, results of a national survey show.

Prior studies show that age- and risk-based standing orders that authorize health care personnel to vaccinate by protocol without physician involvement have increased adult pneumococcal and influenza vaccination rates by 16%–97%, when done as part of a multicomponent strategy.

But unlike assessing adults for pneumococcal disease or influenza, using standing orders to assess for hepatitis B virus (HBV) risk factors requires obtaining potentially sensitive information, Dr. Allison Kempe and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention. Like HIV, HBV can be transmitted through unprotected sex with an infected person or through shared needles.

“This is a debate because some people think that risk-based criteria are far less effective than age-based criteria, and the CDC has decided to go with risk based,” Dr. Kempe, of the Children's Hospital in Denver, said in an interview.

In December 2006, the CDC's Advisory Committee on Immunization Practices recommended, as part of its new comprehensive HBV strategy, that practitioners in primary care settings implement standing orders to identify and vaccinate adults with HBV risk factors.

In September and October 2006, Dr. Kempe and her associates used a mail- or Internet-based questionnaire to survey family medicine and general internal medicine physicians on the feasibility of implementing HBV risk-based standing orders. Surveys were completed by 65% (282 of 433) of family physicians and 79% (332 of 420) general internists. Responses generally did not differ by specialty, so data were combined.

Overall, 47% of respondents reported being “very supportive” and 37% “somewhat supportive” of implementing hepatitis B vaccination of at-risk adults using risk-based standing orders.

“However, physicians reported significant barriers to risk-based approaches, suggesting that alternative strategies might be needed for hepatitis B vaccination to be successfully implemented,” the authors wrote.

Factors identified as “definite barriers” or “somewhat of a barrier” to standing orders included patients not disclosing sensitive information (definite 36%, somewhat 38%); nurses and medical assistants being too pressed for time to assess patients' risk (30%, 37%); risk screening negatively impacting patient flow (20%, 27%); risk screening requiring a higher level of knowledge than nurses or medical assistants have (16%, 30%); and the fact that because of the complexity of the standing orders, nurses and medical assistants would still have questions about who should be immunized (15%, 31%).

The investigators did not perform a head-to-head comparison between risk- and age-based criteria, but feasibility was thought to be higher for age-based criteria, Dr. Kempe said.

Just 25% of family physicians and 27% of internists thought risk-based criteria would be “very feasible” for nurses and medical assistants to implement, compared with 38% and 37% for age-based criteria.

In a second analysis of the same data, most of the family and internal medicine physicians reported that hepatitis B vaccination was a “moderate priority” (42% of the family medicine physicians, 45% of the internists) or a “low priority” (39%, 28%) in their practices, Dr. Matthew Daley and his associates reported in a separate poster at the meeting.

A minority (37%) of respondents routinely use written questionnaires at an initial inpatient visit to assess sexual behavior or drug use, reported Dr. Daley, also of the Children's Hospital.

KANSAS CITY, MO. — Physicians support using risk-based standing orders for adult hepatitis B vaccinations, but see clear barriers to their implementation, results of a national survey show.

Prior studies show that age- and risk-based standing orders that authorize health care personnel to vaccinate by protocol without physician involvement have increased adult pneumococcal and influenza vaccination rates by 16%–97%, when done as part of a multicomponent strategy.

But unlike assessing adults for pneumococcal disease or influenza, using standing orders to assess for hepatitis B virus (HBV) risk factors requires obtaining potentially sensitive information, Dr. Allison Kempe and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention. Like HIV, HBV can be transmitted through unprotected sex with an infected person or through shared needles.

“This is a debate because some people think that risk-based criteria are far less effective than age-based criteria, and the CDC has decided to go with risk based,” Dr. Kempe, of the Children's Hospital in Denver, said in an interview.

In December 2006, the CDC's Advisory Committee on Immunization Practices recommended, as part of its new comprehensive HBV strategy, that practitioners in primary care settings implement standing orders to identify and vaccinate adults with HBV risk factors.

In September and October 2006, Dr. Kempe and her associates used a mail- or Internet-based questionnaire to survey family medicine and general internal medicine physicians on the feasibility of implementing HBV risk-based standing orders. Surveys were completed by 65% (282 of 433) of family physicians and 79% (332 of 420) general internists. Responses generally did not differ by specialty, so data were combined.

Overall, 47% of respondents reported being “very supportive” and 37% “somewhat supportive” of implementing hepatitis B vaccination of at-risk adults using risk-based standing orders.

“However, physicians reported significant barriers to risk-based approaches, suggesting that alternative strategies might be needed for hepatitis B vaccination to be successfully implemented,” the authors wrote.

Factors identified as “definite barriers” or “somewhat of a barrier” to standing orders included patients not disclosing sensitive information (definite 36%, somewhat 38%); nurses and medical assistants being too pressed for time to assess patients' risk (30%, 37%); risk screening negatively impacting patient flow (20%, 27%); risk screening requiring a higher level of knowledge than nurses or medical assistants have (16%, 30%); and the fact that because of the complexity of the standing orders, nurses and medical assistants would still have questions about who should be immunized (15%, 31%).

The investigators did not perform a head-to-head comparison between risk- and age-based criteria, but feasibility was thought to be higher for age-based criteria, Dr. Kempe said.

Just 25% of family physicians and 27% of internists thought risk-based criteria would be “very feasible” for nurses and medical assistants to implement, compared with 38% and 37% for age-based criteria.

In a second analysis of the same data, most of the family and internal medicine physicians reported that hepatitis B vaccination was a “moderate priority” (42% of the family medicine physicians, 45% of the internists) or a “low priority” (39%, 28%) in their practices, Dr. Matthew Daley and his associates reported in a separate poster at the meeting.

A minority (37%) of respondents routinely use written questionnaires at an initial inpatient visit to assess sexual behavior or drug use, reported Dr. Daley, also of the Children's Hospital.

KANSAS CITY, MO. — Physicians support using risk-based standing orders for adult hepatitis B vaccinations, but see clear barriers to their implementation, results of a national survey show.

Prior studies show that age- and risk-based standing orders that authorize health care personnel to vaccinate by protocol without physician involvement have increased adult pneumococcal and influenza vaccination rates by 16%–97%, when done as part of a multicomponent strategy.

But unlike assessing adults for pneumococcal disease or influenza, using standing orders to assess for hepatitis B virus (HBV) risk factors requires obtaining potentially sensitive information, Dr. Allison Kempe and her associates reported in a poster at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention. Like HIV, HBV can be transmitted through unprotected sex with an infected person or through shared needles.

“This is a debate because some people think that risk-based criteria are far less effective than age-based criteria, and the CDC has decided to go with risk based,” Dr. Kempe, of the Children's Hospital in Denver, said in an interview.

In December 2006, the CDC's Advisory Committee on Immunization Practices recommended, as part of its new comprehensive HBV strategy, that practitioners in primary care settings implement standing orders to identify and vaccinate adults with HBV risk factors.

In September and October 2006, Dr. Kempe and her associates used a mail- or Internet-based questionnaire to survey family medicine and general internal medicine physicians on the feasibility of implementing HBV risk-based standing orders. Surveys were completed by 65% (282 of 433) of family physicians and 79% (332 of 420) general internists. Responses generally did not differ by specialty, so data were combined.

Overall, 47% of respondents reported being “very supportive” and 37% “somewhat supportive” of implementing hepatitis B vaccination of at-risk adults using risk-based standing orders.

“However, physicians reported significant barriers to risk-based approaches, suggesting that alternative strategies might be needed for hepatitis B vaccination to be successfully implemented,” the authors wrote.

Factors identified as “definite barriers” or “somewhat of a barrier” to standing orders included patients not disclosing sensitive information (definite 36%, somewhat 38%); nurses and medical assistants being too pressed for time to assess patients' risk (30%, 37%); risk screening negatively impacting patient flow (20%, 27%); risk screening requiring a higher level of knowledge than nurses or medical assistants have (16%, 30%); and the fact that because of the complexity of the standing orders, nurses and medical assistants would still have questions about who should be immunized (15%, 31%).

The investigators did not perform a head-to-head comparison between risk- and age-based criteria, but feasibility was thought to be higher for age-based criteria, Dr. Kempe said.

Just 25% of family physicians and 27% of internists thought risk-based criteria would be “very feasible” for nurses and medical assistants to implement, compared with 38% and 37% for age-based criteria.

In a second analysis of the same data, most of the family and internal medicine physicians reported that hepatitis B vaccination was a “moderate priority” (42% of the family medicine physicians, 45% of the internists) or a “low priority” (39%, 28%) in their practices, Dr. Matthew Daley and his associates reported in a separate poster at the meeting.

A minority (37%) of respondents routinely use written questionnaires at an initial inpatient visit to assess sexual behavior or drug use, reported Dr. Daley, also of the Children's Hospital.

CHICAGO — Self-monitoring of blood glucose did not significantly improve hemoglobin A_1c levels in a trial of patients with type 2 diabetes not receiving insulin.

“Although patients with type 1 and insulin-treated type 2 diabetes benefit from self-monitoring, this trial does not provide convincing evidence of benefit in non-insulin-treated type 2 diabetes,” lead researcher Dr. Andrew J. Farmer said at the annual scientific sessions of the American Diabetes Association. His team conducted the trial, known as DiGEM (Diabetes Glycaemic Education and Monitoring).

Health costs and quality of life data have yet to be presented from the three-arm, randomized, parallel group trial of 453 patients managed in U.K. general practices with diet and oral hypoglycemic agents alone.

“In the meantime, the results do not support recommendations for routine self-monitoring of blood glucose in reasonably well-controlled patients with type 2 diabetes,” said Dr. Farmer, division of public health, University of Oxford (England).

The trial had an 80% power at a 5% level of significance to detect the primary outcome—a change in hemoglobin A_1c of 0.5 percentage points—among three groups. Patients were randomized to a control group with no blood glucose monitors and 3 monthly hemoglobin A_1c measurements; a less intensive self-monitoring group with the results interpreted by a nurse practitioner in addition to usual care; and a more intensive self-monitoring group that was given the usual care plus training in interpreting and applying the results in relation to diet, physical exercise, and medication regimens.

Patients in the more intensive group had more latitude regarding when they could test their glucose, and averaged 6–7 tests per week. Those in the less intensive group were told to use their meters before meals and averaged 5–6 tests per week, Dr. Farmer explained.

There were 152 in the control group, 150 in the less intensive self-monitoring group, and 151 in the more intensive self-monitoring group.

At admission, the average duration of diabetes was 3 years, and the mean HbA_1c was 7.5%. Overall, 67.5%–73% of patients in each of the groups had had no prior experience with self monitoring.

At 12 months, the mean HbA_1c value was 0.14 percentage points lower in the less intensive self-monitoring group than in the control group, and 0.17 percentage points lower in the more intensive self-monitoring group than in the control group. The differences between groups were not statistically significant.

Among secondary outcomes, there were no significant differences between groups in blood pressure control. Surprisingly, there was a significant difference between groups in change from baseline of total cholesterol, with a decrease of 0.14 mmol/L in the control group, 5.2 mmol/L in the less intensive group, and 5.4 mmol/L in the more intensive group.

Hypoglycemia was reported by patients in all three arms of the trial, with the number of reports significantly higher in the self-monitoring groups than in the control group. This finding may be attributable to increased awareness of low blood glucose more than a true biochemical difference arising from the use of the monitor, Dr. Farmer said.

Over the 12 months of the trial, between one-third and one-half of patients stopped using their monitors. In all, 57 patients (13%) were lost to follow-up.

Dr. Farmer speculated that for many patients, the small day-to-day improvement in glucose results may have been obscured by the measurement variation from day to day, and may have contributed to the reason some people gave up. “It's well recognized that, in some people, when the readings don't vary—or seem uninterpretable—[there is] a loss of motivation,” he said.

Interpretation of the DiGEM data will be hotly debated, in part because of the financial implications of self-monitoring on health care agencies and insurers.

The study moves the field ahead, but leaves some questions unanswered, Dr. Bernard Zinman, director of diabetes care at Mount Sinai Hospital, Toronto, said in an interview.

“This study proves definitively that self-monitoring of blood glucose does not seem to have an impact on changing an individual's lifestyle … and therefore [on improving] control,” Dr. Zinman said.

But he added that the investigation didn't address the question of whether, “if you give patients instructions on how to modify their oral hypoglycemia or give their physicians the opportunity to modify [it], self-monitoring of blood glucose may be very valuable in this population.”

CHICAGO — Self-monitoring of blood glucose did not significantly improve hemoglobin A_1c levels in a trial of patients with type 2 diabetes not receiving insulin.

“Although patients with type 1 and insulin-treated type 2 diabetes benefit from self-monitoring, this trial does not provide convincing evidence of benefit in non-insulin-treated type 2 diabetes,” lead researcher Dr. Andrew J. Farmer said at the annual scientific sessions of the American Diabetes Association. His team conducted the trial, known as DiGEM (Diabetes Glycaemic Education and Monitoring).

Health costs and quality of life data have yet to be presented from the three-arm, randomized, parallel group trial of 453 patients managed in U.K. general practices with diet and oral hypoglycemic agents alone.

“In the meantime, the results do not support recommendations for routine self-monitoring of blood glucose in reasonably well-controlled patients with type 2 diabetes,” said Dr. Farmer, division of public health, University of Oxford (England).

The trial had an 80% power at a 5% level of significance to detect the primary outcome—a change in hemoglobin A_1c of 0.5 percentage points—among three groups. Patients were randomized to a control group with no blood glucose monitors and 3 monthly hemoglobin A_1c measurements; a less intensive self-monitoring group with the results interpreted by a nurse practitioner in addition to usual care; and a more intensive self-monitoring group that was given the usual care plus training in interpreting and applying the results in relation to diet, physical exercise, and medication regimens.

Patients in the more intensive group had more latitude regarding when they could test their glucose, and averaged 6–7 tests per week. Those in the less intensive group were told to use their meters before meals and averaged 5–6 tests per week, Dr. Farmer explained.

There were 152 in the control group, 150 in the less intensive self-monitoring group, and 151 in the more intensive self-monitoring group.

At admission, the average duration of diabetes was 3 years, and the mean HbA_1c was 7.5%. Overall, 67.5%–73% of patients in each of the groups had had no prior experience with self monitoring.

At 12 months, the mean HbA_1c value was 0.14 percentage points lower in the less intensive self-monitoring group than in the control group, and 0.17 percentage points lower in the more intensive self-monitoring group than in the control group. The differences between groups were not statistically significant.

Among secondary outcomes, there were no significant differences between groups in blood pressure control. Surprisingly, there was a significant difference between groups in change from baseline of total cholesterol, with a decrease of 0.14 mmol/L in the control group, 5.2 mmol/L in the less intensive group, and 5.4 mmol/L in the more intensive group.

Hypoglycemia was reported by patients in all three arms of the trial, with the number of reports significantly higher in the self-monitoring groups than in the control group. This finding may be attributable to increased awareness of low blood glucose more than a true biochemical difference arising from the use of the monitor, Dr. Farmer said.

Over the 12 months of the trial, between one-third and one-half of patients stopped using their monitors. In all, 57 patients (13%) were lost to follow-up.

Dr. Farmer speculated that for many patients, the small day-to-day improvement in glucose results may have been obscured by the measurement variation from day to day, and may have contributed to the reason some people gave up. “It's well recognized that, in some people, when the readings don't vary—or seem uninterpretable—[there is] a loss of motivation,” he said.

Interpretation of the DiGEM data will be hotly debated, in part because of the financial implications of self-monitoring on health care agencies and insurers.

The study moves the field ahead, but leaves some questions unanswered, Dr. Bernard Zinman, director of diabetes care at Mount Sinai Hospital, Toronto, said in an interview.

“This study proves definitively that self-monitoring of blood glucose does not seem to have an impact on changing an individual's lifestyle … and therefore [on improving] control,” Dr. Zinman said.

But he added that the investigation didn't address the question of whether, “if you give patients instructions on how to modify their oral hypoglycemia or give their physicians the opportunity to modify [it], self-monitoring of blood glucose may be very valuable in this population.”

CHICAGO — Self-monitoring of blood glucose did not significantly improve hemoglobin A_1c levels in a trial of patients with type 2 diabetes not receiving insulin.

“Although patients with type 1 and insulin-treated type 2 diabetes benefit from self-monitoring, this trial does not provide convincing evidence of benefit in non-insulin-treated type 2 diabetes,” lead researcher Dr. Andrew J. Farmer said at the annual scientific sessions of the American Diabetes Association. His team conducted the trial, known as DiGEM (Diabetes Glycaemic Education and Monitoring).

Health costs and quality of life data have yet to be presented from the three-arm, randomized, parallel group trial of 453 patients managed in U.K. general practices with diet and oral hypoglycemic agents alone.

“In the meantime, the results do not support recommendations for routine self-monitoring of blood glucose in reasonably well-controlled patients with type 2 diabetes,” said Dr. Farmer, division of public health, University of Oxford (England).

The trial had an 80% power at a 5% level of significance to detect the primary outcome—a change in hemoglobin A_1c of 0.5 percentage points—among three groups. Patients were randomized to a control group with no blood glucose monitors and 3 monthly hemoglobin A_1c measurements; a less intensive self-monitoring group with the results interpreted by a nurse practitioner in addition to usual care; and a more intensive self-monitoring group that was given the usual care plus training in interpreting and applying the results in relation to diet, physical exercise, and medication regimens.

Patients in the more intensive group had more latitude regarding when they could test their glucose, and averaged 6–7 tests per week. Those in the less intensive group were told to use their meters before meals and averaged 5–6 tests per week, Dr. Farmer explained.

There were 152 in the control group, 150 in the less intensive self-monitoring group, and 151 in the more intensive self-monitoring group.

At admission, the average duration of diabetes was 3 years, and the mean HbA_1c was 7.5%. Overall, 67.5%–73% of patients in each of the groups had had no prior experience with self monitoring.

At 12 months, the mean HbA_1c value was 0.14 percentage points lower in the less intensive self-monitoring group than in the control group, and 0.17 percentage points lower in the more intensive self-monitoring group than in the control group. The differences between groups were not statistically significant.

Among secondary outcomes, there were no significant differences between groups in blood pressure control. Surprisingly, there was a significant difference between groups in change from baseline of total cholesterol, with a decrease of 0.14 mmol/L in the control group, 5.2 mmol/L in the less intensive group, and 5.4 mmol/L in the more intensive group.

Hypoglycemia was reported by patients in all three arms of the trial, with the number of reports significantly higher in the self-monitoring groups than in the control group. This finding may be attributable to increased awareness of low blood glucose more than a true biochemical difference arising from the use of the monitor, Dr. Farmer said.

Over the 12 months of the trial, between one-third and one-half of patients stopped using their monitors. In all, 57 patients (13%) were lost to follow-up.

Dr. Farmer speculated that for many patients, the small day-to-day improvement in glucose results may have been obscured by the measurement variation from day to day, and may have contributed to the reason some people gave up. “It's well recognized that, in some people, when the readings don't vary—or seem uninterpretable—[there is] a loss of motivation,” he said.

Interpretation of the DiGEM data will be hotly debated, in part because of the financial implications of self-monitoring on health care agencies and insurers.

The study moves the field ahead, but leaves some questions unanswered, Dr. Bernard Zinman, director of diabetes care at Mount Sinai Hospital, Toronto, said in an interview.

“This study proves definitively that self-monitoring of blood glucose does not seem to have an impact on changing an individual's lifestyle … and therefore [on improving] control,” Dr. Zinman said.

But he added that the investigation didn't address the question of whether, “if you give patients instructions on how to modify their oral hypoglycemia or give their physicians the opportunity to modify [it], self-monitoring of blood glucose may be very valuable in this population.”

CHICAGO — Lipid-lowering therapy was associated with a significant reduction in the risk of developing peripheral sensory neuropathy in a large Australian observational investigation involving adults with type 2 diabetes mellitus.

Peripheral neuropathy, the most common form of nerve damage caused by diabetes, affects roughly half of those with the disease.

Animal studies have shown that both statins and fibrates may protect against nerve damage, but clinical studies have also linked their use with reversible clinical neuropathy.

The study produced no evidence that use of either statins or fibrates increased the risk of developing neuropathy or amputations, principal investigator Dr. Timothy Davis said at the annual scientific sessions of the American Diabetes Association.

He suggested that previous reports may have been coincidental, in that the individuals were developing neuropathy anyway, or that there may be a small number of patients who were sensitive to the drug.

“Statins and fibrates are relatively safe, but still have a side-effect profile that needs to be respected,” he said. However, statins are typically a first-line drug because of strong evidence of their cardiovascular disease prevention benefits.

The ADA recommends statins for individuals with diabetes aged 40 years and older with a total cholesterol level greater than 135 mg/dL and no overt cardiovascular disease; for those younger than age 40 years with no overt cardiovascular disease, but at increased risk; and for any patient with diabetes and overt cardiovascular disease.

Dr. Davis and colleagues at the University of Western Australia in Fremantle used the Michigan Neuropathy Screening Instrument to determine the prevalence and incidence of peripheral neuropathy in two populations. The first was a cross-sectional sample of 1,294 patients with type 2 diabetes recruited to the Fremantle Diabetes Study between 1993 and 1996.

At admission, fibrates and statins were used by 3.5% and 6.8% of patients, respectively. Gemfibrozil was the fibrate used, and the statins in use were atorvastatin, simvastatin, and pravastatin.

Patients' mean age was 64 years, 49% were male, and 31% had peripheral neuropathy. The median diabetes duration was 4 years.

In multiple logistic regression analysis, older age, longer diabetes duration, central adiposity, increasing height, higher fasting plasma glucose levels, higher systolic blood pressure, higher urinary albumin-to-creatinine ratios, and indigenous racial background were all independently associated with prevalent peripheral neuropathy.

Fibrate use was associated with a 70% reduction in neuropathy, but the use of statins was not associated with a significant reduction in neuropathy, Dr. Davis said.

The investigators then evaluated a longitudinal subgroup of 531 people who had undergone six comprehensive annual health assessments by November 2001. Fibrate and statin use increased to 10.4% and 36.5% during the 5 years of follow-up. Gemfibrozil continued to be the primary fibrate used, although some patients had begun to use fenofibrate. Atorvastatin was the predominant statin. In all, 26% of patients had peripheral neuropathy at baseline.

In a Cox proportional analysis that controlled for a variety of confounding variables, including changes in hemoglobin A_1c levels, fibrates and statins reduced the risk of developing neuropathy by 48% and 35%, respectively.

Analysis of the data also indicated that the beneficial effects of the lipid-lowering drugs were independent of each other and may work through different mechanisms.

“It's possible, because of the independent effect of these drugs, that combination therapy with these drugs could have an additive effect,” Dr. Davis said.

During a press briefing at the meeting, Dr. Aaron I. Vinik, director of the Diabetes Research Institute at Eastern Virginia Medical School, Norfolk, said the data “may change the way clinicians look at neuropathy in the future, and may even change the way we think about treating neuropathy.” The only two drugs approved in the United States for the treatment of neuropathy are for pain relief, and neither addresses the underlying pathogenic disorder of the condition, he said.

Dr. Paul Jellinger, past president of American Association of Clinical Endocrinologists, called the data intriguing, but emphasized that whereas lipid-lowering drugs may prevent the occurrence of neuropathy, they do not reverse it.

If lipid-lowering drugs are to be used for neuropathy prevention, they would have to be introduced early in the disease process, he said.

“To me, the message here is to confirm this evidence with prospective trials, and, if confirmed, to use this as an additional mandate to diagnose impaired glucose tolerance earlier and to consider applying statin or fibrate therapy independent of their lipid levels,” said Dr. Jellinger, who is in private practice in Hollywood, Fla.

CHICAGO — Lipid-lowering therapy was associated with a significant reduction in the risk of developing peripheral sensory neuropathy in a large Australian observational investigation involving adults with type 2 diabetes mellitus.

Peripheral neuropathy, the most common form of nerve damage caused by diabetes, affects roughly half of those with the disease.

Animal studies have shown that both statins and fibrates may protect against nerve damage, but clinical studies have also linked their use with reversible clinical neuropathy.

The study produced no evidence that use of either statins or fibrates increased the risk of developing neuropathy or amputations, principal investigator Dr. Timothy Davis said at the annual scientific sessions of the American Diabetes Association.

He suggested that previous reports may have been coincidental, in that the individuals were developing neuropathy anyway, or that there may be a small number of patients who were sensitive to the drug.

“Statins and fibrates are relatively safe, but still have a side-effect profile that needs to be respected,” he said. However, statins are typically a first-line drug because of strong evidence of their cardiovascular disease prevention benefits.

The ADA recommends statins for individuals with diabetes aged 40 years and older with a total cholesterol level greater than 135 mg/dL and no overt cardiovascular disease; for those younger than age 40 years with no overt cardiovascular disease, but at increased risk; and for any patient with diabetes and overt cardiovascular disease.

Dr. Davis and colleagues at the University of Western Australia in Fremantle used the Michigan Neuropathy Screening Instrument to determine the prevalence and incidence of peripheral neuropathy in two populations. The first was a cross-sectional sample of 1,294 patients with type 2 diabetes recruited to the Fremantle Diabetes Study between 1993 and 1996.

At admission, fibrates and statins were used by 3.5% and 6.8% of patients, respectively. Gemfibrozil was the fibrate used, and the statins in use were atorvastatin, simvastatin, and pravastatin.

Patients' mean age was 64 years, 49% were male, and 31% had peripheral neuropathy. The median diabetes duration was 4 years.

In multiple logistic regression analysis, older age, longer diabetes duration, central adiposity, increasing height, higher fasting plasma glucose levels, higher systolic blood pressure, higher urinary albumin-to-creatinine ratios, and indigenous racial background were all independently associated with prevalent peripheral neuropathy.

Fibrate use was associated with a 70% reduction in neuropathy, but the use of statins was not associated with a significant reduction in neuropathy, Dr. Davis said.

The investigators then evaluated a longitudinal subgroup of 531 people who had undergone six comprehensive annual health assessments by November 2001. Fibrate and statin use increased to 10.4% and 36.5% during the 5 years of follow-up. Gemfibrozil continued to be the primary fibrate used, although some patients had begun to use fenofibrate. Atorvastatin was the predominant statin. In all, 26% of patients had peripheral neuropathy at baseline.

In a Cox proportional analysis that controlled for a variety of confounding variables, including changes in hemoglobin A_1c levels, fibrates and statins reduced the risk of developing neuropathy by 48% and 35%, respectively.

Analysis of the data also indicated that the beneficial effects of the lipid-lowering drugs were independent of each other and may work through different mechanisms.

“It's possible, because of the independent effect of these drugs, that combination therapy with these drugs could have an additive effect,” Dr. Davis said.

During a press briefing at the meeting, Dr. Aaron I. Vinik, director of the Diabetes Research Institute at Eastern Virginia Medical School, Norfolk, said the data “may change the way clinicians look at neuropathy in the future, and may even change the way we think about treating neuropathy.” The only two drugs approved in the United States for the treatment of neuropathy are for pain relief, and neither addresses the underlying pathogenic disorder of the condition, he said.

Dr. Paul Jellinger, past president of American Association of Clinical Endocrinologists, called the data intriguing, but emphasized that whereas lipid-lowering drugs may prevent the occurrence of neuropathy, they do not reverse it.

If lipid-lowering drugs are to be used for neuropathy prevention, they would have to be introduced early in the disease process, he said.

“To me, the message here is to confirm this evidence with prospective trials, and, if confirmed, to use this as an additional mandate to diagnose impaired glucose tolerance earlier and to consider applying statin or fibrate therapy independent of their lipid levels,” said Dr. Jellinger, who is in private practice in Hollywood, Fla.

CHICAGO — Lipid-lowering therapy was associated with a significant reduction in the risk of developing peripheral sensory neuropathy in a large Australian observational investigation involving adults with type 2 diabetes mellitus.

Peripheral neuropathy, the most common form of nerve damage caused by diabetes, affects roughly half of those with the disease.

Animal studies have shown that both statins and fibrates may protect against nerve damage, but clinical studies have also linked their use with reversible clinical neuropathy.

The study produced no evidence that use of either statins or fibrates increased the risk of developing neuropathy or amputations, principal investigator Dr. Timothy Davis said at the annual scientific sessions of the American Diabetes Association.

He suggested that previous reports may have been coincidental, in that the individuals were developing neuropathy anyway, or that there may be a small number of patients who were sensitive to the drug.

“Statins and fibrates are relatively safe, but still have a side-effect profile that needs to be respected,” he said. However, statins are typically a first-line drug because of strong evidence of their cardiovascular disease prevention benefits.

The ADA recommends statins for individuals with diabetes aged 40 years and older with a total cholesterol level greater than 135 mg/dL and no overt cardiovascular disease; for those younger than age 40 years with no overt cardiovascular disease, but at increased risk; and for any patient with diabetes and overt cardiovascular disease.

Dr. Davis and colleagues at the University of Western Australia in Fremantle used the Michigan Neuropathy Screening Instrument to determine the prevalence and incidence of peripheral neuropathy in two populations. The first was a cross-sectional sample of 1,294 patients with type 2 diabetes recruited to the Fremantle Diabetes Study between 1993 and 1996.

At admission, fibrates and statins were used by 3.5% and 6.8% of patients, respectively. Gemfibrozil was the fibrate used, and the statins in use were atorvastatin, simvastatin, and pravastatin.

Patients' mean age was 64 years, 49% were male, and 31% had peripheral neuropathy. The median diabetes duration was 4 years.

In multiple logistic regression analysis, older age, longer diabetes duration, central adiposity, increasing height, higher fasting plasma glucose levels, higher systolic blood pressure, higher urinary albumin-to-creatinine ratios, and indigenous racial background were all independently associated with prevalent peripheral neuropathy.

Fibrate use was associated with a 70% reduction in neuropathy, but the use of statins was not associated with a significant reduction in neuropathy, Dr. Davis said.

The investigators then evaluated a longitudinal subgroup of 531 people who had undergone six comprehensive annual health assessments by November 2001. Fibrate and statin use increased to 10.4% and 36.5% during the 5 years of follow-up. Gemfibrozil continued to be the primary fibrate used, although some patients had begun to use fenofibrate. Atorvastatin was the predominant statin. In all, 26% of patients had peripheral neuropathy at baseline.

In a Cox proportional analysis that controlled for a variety of confounding variables, including changes in hemoglobin A_1c levels, fibrates and statins reduced the risk of developing neuropathy by 48% and 35%, respectively.

Analysis of the data also indicated that the beneficial effects of the lipid-lowering drugs were independent of each other and may work through different mechanisms.

“It's possible, because of the independent effect of these drugs, that combination therapy with these drugs could have an additive effect,” Dr. Davis said.

During a press briefing at the meeting, Dr. Aaron I. Vinik, director of the Diabetes Research Institute at Eastern Virginia Medical School, Norfolk, said the data “may change the way clinicians look at neuropathy in the future, and may even change the way we think about treating neuropathy.” The only two drugs approved in the United States for the treatment of neuropathy are for pain relief, and neither addresses the underlying pathogenic disorder of the condition, he said.

Dr. Paul Jellinger, past president of American Association of Clinical Endocrinologists, called the data intriguing, but emphasized that whereas lipid-lowering drugs may prevent the occurrence of neuropathy, they do not reverse it.

If lipid-lowering drugs are to be used for neuropathy prevention, they would have to be introduced early in the disease process, he said.

“To me, the message here is to confirm this evidence with prospective trials, and, if confirmed, to use this as an additional mandate to diagnose impaired glucose tolerance earlier and to consider applying statin or fibrate therapy independent of their lipid levels,” said Dr. Jellinger, who is in private practice in Hollywood, Fla.

CHICAGO — Despite significant gains in disease control over the last 6 years, nearly half of patients with diabetes failed to reach national treatment goals in 2006.

An analysis of 22.7 million hemoglobin A_1c tests performed on 4.8 million patients with diabetes mellitus revealed that as of December 2006, 55% of patients had reached the American Diabetes Association (ADA) treatment target of hemoglobin A_1c levels less than 7%. This compares with 37.8% in 2001.

The analysis revealed that despite these overall gains, the decline in A_1c values has slowed since 2003, leaving 45% of Americans with diabetes short of ADA targets in 2006.

“For this 45%, we are going to need new approaches to control their diabetes,” coauthor Dr. Richard W. Furlanetto said at a press briefing during the annual scientific sessions of the ADA. “We'll need new medications certainly, but I think we'll need intensive education for these people and new ways of allowing them to live with their disease.”

Roughly 28% of patients with type 1 diabetes reached an A_1c level below 7% in 2001, compared with 35% in 2006. In contrast, 45% and 57% of patients with type 2 diabetes reached the target A_1c over the same time period, said Dr. Furlanetto, a pediatric endocrinologist and medical director of endocrinology at Quest Diagnostics Nichols Institute in Chantilly, Va.

In patients with type 2 diabetes, the overall mean A_1c values declined from 7.6% in 2001 to 7.3% in 2003, but then slowed significantly and stabilized at 7.2% in 2006, according to the analysis of data from the Quest Diagnostics Informatics Data Warehouse, a large private reference laboratory database.

The authors suggest that this HbA_1c plateau mirrors the clinical progression of the disease as well as treatment patterns. Longitudinal analysis indicates that A_1c values for individual patients decreased in the first 1–2 years, and then trended slowly upward. This could be a result of aggressive therapy and strict compliance in the early years, followed by worsening of the disease, which limits therapy, and less diligent treatment compliance, Dr. Furlanetto said.

One of the more striking findings in the study, which was presented as a poster at the meeting, was that A_1c levels show significant seasonal fluctuations, with A_1c levels peaking in the winter between January and March and falling between July and October.

The magnitude of the variation depended on patient age, diabetes type, and winter A_1c value. The variations were most apparent in those aged 80 years and older and those with the highest A_1c levels (9% or more).

HbA_1c measurements taken in late spring and late fall may be more representative of the annual mean A_1c level, Dr. Furlanetto suggested.

While the number of tests reported in the study is more than 50 times that of other published reports on diabetes health, reporters questioned how applicable the findings are to the average patient, given that the sample represents a fraction of the roughly 21 million Americans with diabetes.

Dr. Furlanetto acknowledged that the study was limited by its reliance on ICD-9 billing codes, but countered that the size of the database was substantial; that it covered all 50 states, the District of Columbia, and Puerto Rico; and that it may actually underrepresent the number of patients under the care of endocrinologists.

Session moderator Martha M. Funnell, a registered nurse and certified diabetes educator at the University of Michigan, Ann Arbor, said one of the strengths of the study was its size. “I realize it's not 100% of people with diabetes, but it's a very, very robust representation,” she said. Additionally, the patient population was a random sample, and the study underrepresented endocrinologists, who would presumably provide better diabetes management, she added.

CHICAGO — Despite significant gains in disease control over the last 6 years, nearly half of patients with diabetes failed to reach national treatment goals in 2006.

An analysis of 22.7 million hemoglobin A_1c tests performed on 4.8 million patients with diabetes mellitus revealed that as of December 2006, 55% of patients had reached the American Diabetes Association (ADA) treatment target of hemoglobin A_1c levels less than 7%. This compares with 37.8% in 2001.

The analysis revealed that despite these overall gains, the decline in A_1c values has slowed since 2003, leaving 45% of Americans with diabetes short of ADA targets in 2006.

“For this 45%, we are going to need new approaches to control their diabetes,” coauthor Dr. Richard W. Furlanetto said at a press briefing during the annual scientific sessions of the ADA. “We'll need new medications certainly, but I think we'll need intensive education for these people and new ways of allowing them to live with their disease.”

Roughly 28% of patients with type 1 diabetes reached an A_1c level below 7% in 2001, compared with 35% in 2006. In contrast, 45% and 57% of patients with type 2 diabetes reached the target A_1c over the same time period, said Dr. Furlanetto, a pediatric endocrinologist and medical director of endocrinology at Quest Diagnostics Nichols Institute in Chantilly, Va.

In patients with type 2 diabetes, the overall mean A_1c values declined from 7.6% in 2001 to 7.3% in 2003, but then slowed significantly and stabilized at 7.2% in 2006, according to the analysis of data from the Quest Diagnostics Informatics Data Warehouse, a large private reference laboratory database.

The authors suggest that this HbA_1c plateau mirrors the clinical progression of the disease as well as treatment patterns. Longitudinal analysis indicates that A_1c values for individual patients decreased in the first 1–2 years, and then trended slowly upward. This could be a result of aggressive therapy and strict compliance in the early years, followed by worsening of the disease, which limits therapy, and less diligent treatment compliance, Dr. Furlanetto said.

One of the more striking findings in the study, which was presented as a poster at the meeting, was that A_1c levels show significant seasonal fluctuations, with A_1c levels peaking in the winter between January and March and falling between July and October.

The magnitude of the variation depended on patient age, diabetes type, and winter A_1c value. The variations were most apparent in those aged 80 years and older and those with the highest A_1c levels (9% or more).

HbA_1c measurements taken in late spring and late fall may be more representative of the annual mean A_1c level, Dr. Furlanetto suggested.

While the number of tests reported in the study is more than 50 times that of other published reports on diabetes health, reporters questioned how applicable the findings are to the average patient, given that the sample represents a fraction of the roughly 21 million Americans with diabetes.

Dr. Furlanetto acknowledged that the study was limited by its reliance on ICD-9 billing codes, but countered that the size of the database was substantial; that it covered all 50 states, the District of Columbia, and Puerto Rico; and that it may actually underrepresent the number of patients under the care of endocrinologists.

Session moderator Martha M. Funnell, a registered nurse and certified diabetes educator at the University of Michigan, Ann Arbor, said one of the strengths of the study was its size. “I realize it's not 100% of people with diabetes, but it's a very, very robust representation,” she said. Additionally, the patient population was a random sample, and the study underrepresented endocrinologists, who would presumably provide better diabetes management, she added.

CHICAGO — Despite significant gains in disease control over the last 6 years, nearly half of patients with diabetes failed to reach national treatment goals in 2006.

An analysis of 22.7 million hemoglobin A_1c tests performed on 4.8 million patients with diabetes mellitus revealed that as of December 2006, 55% of patients had reached the American Diabetes Association (ADA) treatment target of hemoglobin A_1c levels less than 7%. This compares with 37.8% in 2001.

The analysis revealed that despite these overall gains, the decline in A_1c values has slowed since 2003, leaving 45% of Americans with diabetes short of ADA targets in 2006.

“For this 45%, we are going to need new approaches to control their diabetes,” coauthor Dr. Richard W. Furlanetto said at a press briefing during the annual scientific sessions of the ADA. “We'll need new medications certainly, but I think we'll need intensive education for these people and new ways of allowing them to live with their disease.”

Roughly 28% of patients with type 1 diabetes reached an A_1c level below 7% in 2001, compared with 35% in 2006. In contrast, 45% and 57% of patients with type 2 diabetes reached the target A_1c over the same time period, said Dr. Furlanetto, a pediatric endocrinologist and medical director of endocrinology at Quest Diagnostics Nichols Institute in Chantilly, Va.

In patients with type 2 diabetes, the overall mean A_1c values declined from 7.6% in 2001 to 7.3% in 2003, but then slowed significantly and stabilized at 7.2% in 2006, according to the analysis of data from the Quest Diagnostics Informatics Data Warehouse, a large private reference laboratory database.

The authors suggest that this HbA_1c plateau mirrors the clinical progression of the disease as well as treatment patterns. Longitudinal analysis indicates that A_1c values for individual patients decreased in the first 1–2 years, and then trended slowly upward. This could be a result of aggressive therapy and strict compliance in the early years, followed by worsening of the disease, which limits therapy, and less diligent treatment compliance, Dr. Furlanetto said.

One of the more striking findings in the study, which was presented as a poster at the meeting, was that A_1c levels show significant seasonal fluctuations, with A_1c levels peaking in the winter between January and March and falling between July and October.

The magnitude of the variation depended on patient age, diabetes type, and winter A_1c value. The variations were most apparent in those aged 80 years and older and those with the highest A_1c levels (9% or more).

HbA_1c measurements taken in late spring and late fall may be more representative of the annual mean A_1c level, Dr. Furlanetto suggested.

While the number of tests reported in the study is more than 50 times that of other published reports on diabetes health, reporters questioned how applicable the findings are to the average patient, given that the sample represents a fraction of the roughly 21 million Americans with diabetes.

Dr. Furlanetto acknowledged that the study was limited by its reliance on ICD-9 billing codes, but countered that the size of the database was substantial; that it covered all 50 states, the District of Columbia, and Puerto Rico; and that it may actually underrepresent the number of patients under the care of endocrinologists.

Session moderator Martha M. Funnell, a registered nurse and certified diabetes educator at the University of Michigan, Ann Arbor, said one of the strengths of the study was its size. “I realize it's not 100% of people with diabetes, but it's a very, very robust representation,” she said. Additionally, the patient population was a random sample, and the study underrepresented endocrinologists, who would presumably provide better diabetes management, she added.

CHICAGO — Nearly three-fourths of patients with uncontrolled hypertension on monotherapy achieved national blood pressure targets on a fixed-dose combination of amlodipine and valsartan that will soon be available, Dr. Joseph L. Izzo Jr. reported at the annual meeting of the American Society of Hypertension.

Two different formulations of Novartis' single-tablet combination drug, which was approved in June and will be marketed as Exforge, were evaluated in a double-blind, multicenter study that randomized 443 patients to amlodipine 5 mg/valsartan 160 mg and 451 patients to amlodipine 10 mg/valsartan 160 mg. After 8 weeks, hydrochlorothiazide (HCTZ) could be added on, first at 12.5 mg, and then at 25 mg.

The majority of patients, including 145 (16%) of whom had type 2 diabetes, had been previously treated with a β-blocker, angiotensin receptor antagonist, ACE inhibitor, calcium channel blocker, or diuretic.

At admission, their mean age was 58 years, more than 90% were white, and their mean BP was 150/90 mm Hg, said Dr. Izzo, who has received research support and is a consultant for Novartis, which sponsored the study.

The study's primary end point was the proportion of patients after 8 and 16 weeks who had reached a BP of 140/90 mm Hg or 130/80 mm Hg for those with diabetes—the currently recommended dual BP targets in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7).

In an intent-to-treat analysis at week 16, 322 of 440 patients (73%) on the 5- mg/160-mg dose and 338 of 449 patients (75%) on the 10-mg/160-mg dose achieved the dual JNC7 targets, the investigators reported.

Among those with diabetes, 25 of the 61 patients (41%) on the low-dose combination and 27 of the 59 patients (46%) on the high-dose combination reached a BP of less than 130 mm Hg.

Switching patients to the combination therapy resulted in an average additional 20-mm Hg drop in systolic BP, compared with reductions seen with their previous medications. said Dr. Izzo, professor of medicine, State University of New York at Buffalo, said at a press briefing.

BP control rates were similar when stratified by prior medication, age, or ethnicity. There was little increased response after 8 weeks that could be attributed to the addition of HCTZ therapy.

Adverse events were similar between groups, although the incidence of edema was higher with the 10-mg/160-mg dose than with the lower dose (25% vs. 8%).

Exforge was approved by the Food and Drug Administration last month. It is indicated for the treatment of hypertension in patients whose blood pressure has not been adequately controlled with a calcium channel blocker or angiotensin II receptor blocker alone. The pills will be available in four strengths: 5 mg amlodipine/60 mg valsartan, 10 mg/160 mg, 5 mg/320 mg, and 10 mg/320 mg. Exforge has been launched by Novartis in select European countries. The products will be available in the United States no earlier than Sept. 25 of this year, the FDA specified in a December 2006 letter to Novartis, because amlodipine (Norvasc, Pfizer) remains under patent protection until then.

CHICAGO — Nearly three-fourths of patients with uncontrolled hypertension on monotherapy achieved national blood pressure targets on a fixed-dose combination of amlodipine and valsartan that will soon be available, Dr. Joseph L. Izzo Jr. reported at the annual meeting of the American Society of Hypertension.

Two different formulations of Novartis' single-tablet combination drug, which was approved in June and will be marketed as Exforge, were evaluated in a double-blind, multicenter study that randomized 443 patients to amlodipine 5 mg/valsartan 160 mg and 451 patients to amlodipine 10 mg/valsartan 160 mg. After 8 weeks, hydrochlorothiazide (HCTZ) could be added on, first at 12.5 mg, and then at 25 mg.

The majority of patients, including 145 (16%) of whom had type 2 diabetes, had been previously treated with a β-blocker, angiotensin receptor antagonist, ACE inhibitor, calcium channel blocker, or diuretic.

At admission, their mean age was 58 years, more than 90% were white, and their mean BP was 150/90 mm Hg, said Dr. Izzo, who has received research support and is a consultant for Novartis, which sponsored the study.

The study's primary end point was the proportion of patients after 8 and 16 weeks who had reached a BP of 140/90 mm Hg or 130/80 mm Hg for those with diabetes—the currently recommended dual BP targets in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7).

In an intent-to-treat analysis at week 16, 322 of 440 patients (73%) on the 5- mg/160-mg dose and 338 of 449 patients (75%) on the 10-mg/160-mg dose achieved the dual JNC7 targets, the investigators reported.

Among those with diabetes, 25 of the 61 patients (41%) on the low-dose combination and 27 of the 59 patients (46%) on the high-dose combination reached a BP of less than 130 mm Hg.

Switching patients to the combination therapy resulted in an average additional 20-mm Hg drop in systolic BP, compared with reductions seen with their previous medications. said Dr. Izzo, professor of medicine, State University of New York at Buffalo, said at a press briefing.

BP control rates were similar when stratified by prior medication, age, or ethnicity. There was little increased response after 8 weeks that could be attributed to the addition of HCTZ therapy.

Adverse events were similar between groups, although the incidence of edema was higher with the 10-mg/160-mg dose than with the lower dose (25% vs. 8%).

Exforge was approved by the Food and Drug Administration last month. It is indicated for the treatment of hypertension in patients whose blood pressure has not been adequately controlled with a calcium channel blocker or angiotensin II receptor blocker alone. The pills will be available in four strengths: 5 mg amlodipine/60 mg valsartan, 10 mg/160 mg, 5 mg/320 mg, and 10 mg/320 mg. Exforge has been launched by Novartis in select European countries. The products will be available in the United States no earlier than Sept. 25 of this year, the FDA specified in a December 2006 letter to Novartis, because amlodipine (Norvasc, Pfizer) remains under patent protection until then.

CHICAGO — Nearly three-fourths of patients with uncontrolled hypertension on monotherapy achieved national blood pressure targets on a fixed-dose combination of amlodipine and valsartan that will soon be available, Dr. Joseph L. Izzo Jr. reported at the annual meeting of the American Society of Hypertension.

Two different formulations of Novartis' single-tablet combination drug, which was approved in June and will be marketed as Exforge, were evaluated in a double-blind, multicenter study that randomized 443 patients to amlodipine 5 mg/valsartan 160 mg and 451 patients to amlodipine 10 mg/valsartan 160 mg. After 8 weeks, hydrochlorothiazide (HCTZ) could be added on, first at 12.5 mg, and then at 25 mg.

The majority of patients, including 145 (16%) of whom had type 2 diabetes, had been previously treated with a β-blocker, angiotensin receptor antagonist, ACE inhibitor, calcium channel blocker, or diuretic.

At admission, their mean age was 58 years, more than 90% were white, and their mean BP was 150/90 mm Hg, said Dr. Izzo, who has received research support and is a consultant for Novartis, which sponsored the study.

The study's primary end point was the proportion of patients after 8 and 16 weeks who had reached a BP of 140/90 mm Hg or 130/80 mm Hg for those with diabetes—the currently recommended dual BP targets in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7).

In an intent-to-treat analysis at week 16, 322 of 440 patients (73%) on the 5- mg/160-mg dose and 338 of 449 patients (75%) on the 10-mg/160-mg dose achieved the dual JNC7 targets, the investigators reported.

Among those with diabetes, 25 of the 61 patients (41%) on the low-dose combination and 27 of the 59 patients (46%) on the high-dose combination reached a BP of less than 130 mm Hg.

Switching patients to the combination therapy resulted in an average additional 20-mm Hg drop in systolic BP, compared with reductions seen with their previous medications. said Dr. Izzo, professor of medicine, State University of New York at Buffalo, said at a press briefing.

BP control rates were similar when stratified by prior medication, age, or ethnicity. There was little increased response after 8 weeks that could be attributed to the addition of HCTZ therapy.

Adverse events were similar between groups, although the incidence of edema was higher with the 10-mg/160-mg dose than with the lower dose (25% vs. 8%).

Exforge was approved by the Food and Drug Administration last month. It is indicated for the treatment of hypertension in patients whose blood pressure has not been adequately controlled with a calcium channel blocker or angiotensin II receptor blocker alone. The pills will be available in four strengths: 5 mg amlodipine/60 mg valsartan, 10 mg/160 mg, 5 mg/320 mg, and 10 mg/320 mg. Exforge has been launched by Novartis in select European countries. The products will be available in the United States no earlier than Sept. 25 of this year, the FDA specified in a December 2006 letter to Novartis, because amlodipine (Norvasc, Pfizer) remains under patent protection until then.

CHICAGO — The angiotensin II blocker losartan, alone or in combination with the diuretic hydrochlorothiazide, appears efficacious in the treatment of obesity-associated hypertension, new data suggest.

Current guidelines—based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)—do not specify particular treatments for obesity-related hypertension or for the related metabolic syndrome.

The prominent role of angiotensin II in obesity-induced hypertension, however, suggests the possibility that angiotensin receptor blockade may be useful in its treatment, Dr. Suzanne Oparil said at the annual meeting of the American Society of Hypertension (ASH).

She presented preliminary data from a double-blind trial in which 261 patients from 51 sites were randomized to either placebo or losartan 50 mg/day for 4 weeks, titrated to 100 mg/day. Hydrochlorothiazide 12.5 mg/day was added in the active treatment group at week 8 and titrated to 25 mg/day at week 12.

At admission, the average body mass index was 37 kg/m

In all, 105 patients in each group completed the study, which was sponsored by Merck & Co. Inc., which has provided research support to Dr. Oparil.

Losartan 50 mg reduced the average sitting systolic BP to 140 mm Hg at week 4 and maintained it there through week 8. Adding hydrochlorothiazide to the 100-mg losartan dosage caused significant further reductions to about 133 mm Hg at week 16.

Similarly, losartan 50 mg decreased the average sitting diastolic BP to 90 mm Hg at week 4 through week 8. Add-on hydrochlorothiazide decreased the diastolic BP reading to about 85 mm Hg at week 18.

At week 16, 75% of patients on losartan achieved systolic BP control to less than 140 mm Hg, and 77% achieved diastolic BP control to less than 90 mm Hg.

In comparison, control rates for patients on placebo were 18% for systolic BP and 38% for diastolic.

All changes in the losartan group were significantly greater than those in the placebo group for all time points, said Dr. Oparil, president of the ASH and director of the vascular biology and hypertension program at the University of Alabama, Birmingham.

The losartan-based treatment regimen had a similar safety and tolerability profile as placebo, she said.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — The angiotensin II blocker losartan, alone or in combination with the diuretic hydrochlorothiazide, appears efficacious in the treatment of obesity-associated hypertension, new data suggest.

Current guidelines—based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)—do not specify particular treatments for obesity-related hypertension or for the related metabolic syndrome.

The prominent role of angiotensin II in obesity-induced hypertension, however, suggests the possibility that angiotensin receptor blockade may be useful in its treatment, Dr. Suzanne Oparil said at the annual meeting of the American Society of Hypertension (ASH).

She presented preliminary data from a double-blind trial in which 261 patients from 51 sites were randomized to either placebo or losartan 50 mg/day for 4 weeks, titrated to 100 mg/day. Hydrochlorothiazide 12.5 mg/day was added in the active treatment group at week 8 and titrated to 25 mg/day at week 12.

At admission, the average body mass index was 37 kg/m

In all, 105 patients in each group completed the study, which was sponsored by Merck & Co. Inc., which has provided research support to Dr. Oparil.

Losartan 50 mg reduced the average sitting systolic BP to 140 mm Hg at week 4 and maintained it there through week 8. Adding hydrochlorothiazide to the 100-mg losartan dosage caused significant further reductions to about 133 mm Hg at week 16.

Similarly, losartan 50 mg decreased the average sitting diastolic BP to 90 mm Hg at week 4 through week 8. Add-on hydrochlorothiazide decreased the diastolic BP reading to about 85 mm Hg at week 18.

At week 16, 75% of patients on losartan achieved systolic BP control to less than 140 mm Hg, and 77% achieved diastolic BP control to less than 90 mm Hg.

In comparison, control rates for patients on placebo were 18% for systolic BP and 38% for diastolic.

All changes in the losartan group were significantly greater than those in the placebo group for all time points, said Dr. Oparil, president of the ASH and director of the vascular biology and hypertension program at the University of Alabama, Birmingham.

The losartan-based treatment regimen had a similar safety and tolerability profile as placebo, she said.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — The angiotensin II blocker losartan, alone or in combination with the diuretic hydrochlorothiazide, appears efficacious in the treatment of obesity-associated hypertension, new data suggest.

Current guidelines—based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)—do not specify particular treatments for obesity-related hypertension or for the related metabolic syndrome.

The prominent role of angiotensin II in obesity-induced hypertension, however, suggests the possibility that angiotensin receptor blockade may be useful in its treatment, Dr. Suzanne Oparil said at the annual meeting of the American Society of Hypertension (ASH).

She presented preliminary data from a double-blind trial in which 261 patients from 51 sites were randomized to either placebo or losartan 50 mg/day for 4 weeks, titrated to 100 mg/day. Hydrochlorothiazide 12.5 mg/day was added in the active treatment group at week 8 and titrated to 25 mg/day at week 12.

At admission, the average body mass index was 37 kg/m

In all, 105 patients in each group completed the study, which was sponsored by Merck & Co. Inc., which has provided research support to Dr. Oparil.

Losartan 50 mg reduced the average sitting systolic BP to 140 mm Hg at week 4 and maintained it there through week 8. Adding hydrochlorothiazide to the 100-mg losartan dosage caused significant further reductions to about 133 mm Hg at week 16.

Similarly, losartan 50 mg decreased the average sitting diastolic BP to 90 mm Hg at week 4 through week 8. Add-on hydrochlorothiazide decreased the diastolic BP reading to about 85 mm Hg at week 18.

At week 16, 75% of patients on losartan achieved systolic BP control to less than 140 mm Hg, and 77% achieved diastolic BP control to less than 90 mm Hg.

In comparison, control rates for patients on placebo were 18% for systolic BP and 38% for diastolic.

All changes in the losartan group were significantly greater than those in the placebo group for all time points, said Dr. Oparil, president of the ASH and director of the vascular biology and hypertension program at the University of Alabama, Birmingham.

The losartan-based treatment regimen had a similar safety and tolerability profile as placebo, she said.

ELSEVIER GLOBAL MEDICAL NEWS